ABSTRACT Support is requested for a Keystone Symposia conference entitled Protein Replacement through Nucleic Acid Therapies, organized by Drs. Pad Chivukula, Melissa J. Moore and Jean Bennett. The conference will be held in Steamboat Springs, Colorado from April 7-10, 2019. Protein replacement therapy based on recombinant protein has so far been limited to genetic diseases in which the mutated protein acts extracellularly. Nucleic acid therapies such as gene therapy and messenger RNA enable replacement of intracellular proteins, or extracellular proteins too complex to manufacture. This opens up the potential to treat many previously unapproachable diseases. After early setbacks in gene therapy, a new generation of therapeutics are showing progress in the clinic. Novel messenger RNA and RNA delivery technologies are also in development, the potential of which is only beginning to be demonstrated. These represent exciting areas of therapeutic development which also touch on fundamental questions about regulation of gene expression, protein production, and immunity. This conference brings these communities together to discuss common challenges and complementarities, providing an opportunity for cross-fertilization.